The current study is a 52-week safety study in elderly outpatients with chronic primary insomnia randomized to treatment with 1.5 mg or 3.0 mg of Org 50081 to investigate the safety and tolerability of long-term treatment with Org 50081 in elderly patients.

Insomnia is a common complaint or disorder throughout the world. About one third of the population in the industrial countries reports difficulty initiating or maintaining sleep, resulting in a non-refreshing or non-restorative sleep. The majority of the insomniacs suffer chronically from their complaints.

The maleic acid salt of Org 4420, code name Org 50081, was selected for development in the treatment of insomnia. The first clinical trial with Org 50081 was a proof-of-concept trial with a four-way cross-over design. All 3 Org 50081 dose groups showed a statistically significant positive effect on TST (objective and subjective) and WASO, as compared to placebo.

The current study is a 52-week safety study in elderly outpatients with chronic primary insomnia randomized to treatment with 1.5 mg or 3.0 mg of Org 50081 50081 to investigate the safety and tolerability of long-term treatment with Org 50081 in elderly patients.

Inclusion Criteria:

• are at least 65 years of age at screening;
• sign written informed consent after the scope and nature of the investigation have been explained to them, before screening evaluations;
• are able to speak, read and understand the language of the investigator, study staff (including raters) and the informed consent form, and possess the ability to respond to questions, follow instructions and complete questionnaires;
• have demonstrated capability to independently complete the LogPad questionnaires in the week preceding randomization;
• normal bedtime should be within the 21:00 - 01:00 hour range, with no more variation than 2 hours for 5 nights out of 7;
• have a documented diagnosis of chronic primary insomnia, defined as fulfillment of the DSM-IV-TR criteria for primary insomnia (DSM-IV-TR 307.42) with a duration of >= 1 month;

• fulfill the following criteria based on medical or sleep history. Each of these criteria should be present for at least 3 nights per week for at least one month;

  • TST <= 6.5 hours
  • WASO >= 60 minutes
  • SL >= 30 minutes

Exclusion Criteria:

• have other sleep disorders (DSM-IV-TR) e.g. rapid eye movement (REM) behavioral disorders, sleep related breathing disorders, periodic leg movement disorder, restless leg syndrome, narcolepsy, circadian sleep wake rhythm disorders, or any parasomnia;
• have any significant medical or DSM-IV-TR psychiatric illness causing the sleep disturbances;
• currently meet diagnostic criteria for DSM-IV-TR depression (MDD) or have been diagnosed and treated for MDD within the last 2 years;
• have signs of dementia or other serious cognitive impairment, defined by a score of less than 26 on the Mini-Mental State Examination (MMSE);
• have a history of bipolar disorder, a history of suicide attempt or a family history of suicide; A family history of suicide is defined as any history of suicide in the first and second degree family (parents, siblings, grandparents, or offspring), or a pattern of completed suicides (more than one) in the third degree family (aunts, uncles, nieces, and nephews);
• are night workers or rotating shift workers;
• are traveling, or have plans to travel, through more than three time zones during the trial, from the screening visit onwards;
• have a significant, unstable medical illness e.g. acute or chronic pain, hepatic, renal, metabolic or cardiac disease;
• have clinically relevant ECG abnormalities at screening, as judged by the investigator;
• have clinically relevant abnormal hematology or biochemistry values at screening, as judged by the investigator;
• have DSM-IV-TR substance abuse or DSM-IV-TR addiction within the last year;
• drink more than 2 alcoholic drinks in a day. One drink is approximately equal to: 12 oz or 360 ml of beer (regular or light), or 4 oz or 120 ml of red or white wine, or 2 oz or 60 ml of desert wine (e.g. port, sherry), or 12 oz or 360 ml of wine cooler (regular or light), or 1 oz or 30 ml or spirits (80 to 100 proof, e.g. whiskey, vodka);
• had serious head injury or stroke within the past year, or a history of (non-febrile) seizures;
• use psychotropic drugs affecting sleep within 2 weeks prior to randomization (fluoxetine: 5 weeks);
• use concomitant medication affecting sleep (see Protocol Section 3.4, Concomitant medication);
• smoke > 15 cigarettes per day and/or can not abstain from smoking during the night;
• drink excessive amounts of caffeinated beverages (more than 500 mg caffeine per day);
• have a positive urine drug screen at screening;
• are routinely sleeping during daytime (napping) for more than 60 minutes per day, 3 times/ week;
• have a body mass index (BMI) >= 36;
• have a known hypersensitivity to mirtazapine or to any of the excipients;
• participated in another clinical trial within the last 30 days prior to screening;
• participated in another clinical trial using esmirtazapine (Org 50081) at any time.